The purpose of the proposed investigation is to determine the principles which govern synaptic specificity and plasticity. The superior cervical sympathetic ganglion of the rat is the system chosen for study, since it provides the opportunity to compare the interactions between the pre- and postsynaptic neurons under several different conditions. These conditions are normal development, regeneration after preganglionic denervation, collateral sprouting by foreign axons after preganglionic denervation, and synapse removal and restoration after postganglionic axotomy. The ganglia will be analyzed primarily by quantitative electron microscopy with particular emphasis on the interactions between the presynaptic terminals and the postsynaptic membrane specializations during synaptogenesis. In addition, a portion of the proposed study will be concerned with the development of valid and reliable methods for the ultrastructural localization of the ganglionic cholinergic receptors and their role in synaptogenesis. The results obtained from the proposed investigation will contribute toward understanding the constraints imposed by the pre- and postsynaptic neurons during the synapse formation which occurs in normal development and after injury to the nervous system.